hi they stop it unless you want cancer bexarotene the one the other one it On going by 2025 we have this drugs in m.s
i use it now
Summary of the pipeline
Frexalimab phase 2 trial
Inhibition of CD40L with Frexalimab in Multiple Sclerosis
N Engl J Med. 2024 Feb 15;390(7):589-600.
Background: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.
Methods: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab.
Results: Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches.
Conclusions: In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628).
N Engl J Med. 2024 Feb 15;390(7):589-600.
Background: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.
Methods: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab.
Results: Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches.
Conclusions: In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628).
Re: AICAR
This is from 2019.
What Athletes Should Know About AICAR and Other Prohibited AMP Activated Protein Kinase Activators
Education, Spirit of Sport / November 14, 2019
https://www.usada.org/spirit-of-sport/e ... ctivators/
In recent years, AICAR has been in the news a number of times as a novel substance athletes have turned to for performance enhancement. However, this substance is both prohibited in sport and a health risk because it’s not approved for therapeutic use in humans anywhere in the world.
Here’s what athletes should know about AICAR and other prohibited AMP activated protein kinase activators.
What is AICAR?
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a substance produced naturally by the body that stimulates AMP activated protein kinase (AMPK), a protein that regulates metabolism in a variety of ways. AMPK acts as an energy regulator and is activated during exercise or other circumstances that use up cellular energy.
The AMPK-stimulating AICAR can also be synthesized in a lab and is being evaluated in preclinical research and human clinical trials as a therapeutic agent to treat certain metabolic disorders in humans.
How do AICAR and AMPK impact performance?
Once activated by AICAR, AMPK works to make energy more available. For example, it increases the usage of fat for energy and causes cells to make more mitochondria (the cells’ powerhouses or energy creators). AMPK basically ensures that the various tissues in the body don’t run out of energy.
There are many circumstances that activate AMPK naturally, including hypoxia (low oxygen levels during exercise or at elevation), hypoglycemia (low blood sugar with exercise or fasting), the use of cellular energy during muscle contraction, and anything that disrupts energy creation within cells.
The effects of activating AMPK are extremely complex since it is involved in so many different metabolic pathways of the body. To date, the medical community has not found a way to target AMPK in a way that allows for the treatment of diseases in humans, although research has suggested it plays a role in diabetes, heart disease, and cancer.
Why is AICAR on the World Anti-Doping Agency (WADA) Prohibited List?
AICAR is prohibited because it’s an AMPK activator, which are prohibited at all times under the category of Hormone and Metabolic Modulators on the WADA Prohibited List because of their potential performance-enhancing effects.
Are there health risks to using AICAR?
Some articles refer to AMPK activators as “exercise-in-a-pill” in the hope that using an AMPK activator will cause the same changes in the body as exercise. However, the truth is much more complex.
Too much activation of AMPK, or activating it in the wrong tissue, can cause serious side effects, including neurodegeneration, or preventing cells from dividing. The accumulation of naturally-occurring AICAR in the body is also associated with metabolic disorders in humans.
However, AICAR has not been extensively studied in people. For this reason and many others, AICAR is an experimental compound that is not yet approved for therapeutic use in humans and should not be used by any athletes.
Can I get a TUE for AICAR?
No, athletes cannot get a TUE for AICAR because it is not approved for use in humans anywhere in the world. AICAR is not available as a medication, so your doctor should not prescribe it for you under any circumstance.
What Athletes Should Know About AICAR and Other Prohibited AMP Activated Protein Kinase Activators
Education, Spirit of Sport / November 14, 2019
https://www.usada.org/spirit-of-sport/e ... ctivators/
In recent years, AICAR has been in the news a number of times as a novel substance athletes have turned to for performance enhancement. However, this substance is both prohibited in sport and a health risk because it’s not approved for therapeutic use in humans anywhere in the world.
Here’s what athletes should know about AICAR and other prohibited AMP activated protein kinase activators.
What is AICAR?
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a substance produced naturally by the body that stimulates AMP activated protein kinase (AMPK), a protein that regulates metabolism in a variety of ways. AMPK acts as an energy regulator and is activated during exercise or other circumstances that use up cellular energy.
The AMPK-stimulating AICAR can also be synthesized in a lab and is being evaluated in preclinical research and human clinical trials as a therapeutic agent to treat certain metabolic disorders in humans.
How do AICAR and AMPK impact performance?
Once activated by AICAR, AMPK works to make energy more available. For example, it increases the usage of fat for energy and causes cells to make more mitochondria (the cells’ powerhouses or energy creators). AMPK basically ensures that the various tissues in the body don’t run out of energy.
There are many circumstances that activate AMPK naturally, including hypoxia (low oxygen levels during exercise or at elevation), hypoglycemia (low blood sugar with exercise or fasting), the use of cellular energy during muscle contraction, and anything that disrupts energy creation within cells.
The effects of activating AMPK are extremely complex since it is involved in so many different metabolic pathways of the body. To date, the medical community has not found a way to target AMPK in a way that allows for the treatment of diseases in humans, although research has suggested it plays a role in diabetes, heart disease, and cancer.
Why is AICAR on the World Anti-Doping Agency (WADA) Prohibited List?
AICAR is prohibited because it’s an AMPK activator, which are prohibited at all times under the category of Hormone and Metabolic Modulators on the WADA Prohibited List because of their potential performance-enhancing effects.
Are there health risks to using AICAR?
Some articles refer to AMPK activators as “exercise-in-a-pill” in the hope that using an AMPK activator will cause the same changes in the body as exercise. However, the truth is much more complex.
Too much activation of AMPK, or activating it in the wrong tissue, can cause serious side effects, including neurodegeneration, or preventing cells from dividing. The accumulation of naturally-occurring AICAR in the body is also associated with metabolic disorders in humans.
However, AICAR has not been extensively studied in people. For this reason and many others, AICAR is an experimental compound that is not yet approved for therapeutic use in humans and should not be used by any athletes.
Can I get a TUE for AICAR?
No, athletes cannot get a TUE for AICAR because it is not approved for use in humans anywhere in the world. AICAR is not available as a medication, so your doctor should not prescribe it for you under any circumstance.